Methods for producing alkyl hydroxyalkanoates

ABSTRACT

Methods and systems for producing alkyl hydroxyalkanoate from hydroxy carboxylic acid recovery bottoms. The methods generally comprise the steps of obtaining a hydroxy carboxylic acid recovery bottom, adding a mono-alcohol to the hydroxy carboxylic acid recovery bottom to obtain a first mixture, heating the first mixture in the presence of a catalyst to form a reaction product, distilling the reaction product, and recovering an alkyl hydroxyalkanoate fraction.

This application is a Continuation of U.S. patent application Ser. No.15/029,357, filed Apr. 14, 2016, entitled METHODS FOR PRODUCING ALKYLHYDROXYALKA.NOATES, now U.S. Pat. No. 9,938,224 which is a nationalphase application of International Application PCT/US2014/061192, filedOct. 17, 2014, entitled METHODS FOR PRODUCING ALKYL HYDROXYALKANOATES,which application claims the benefit of the U.S. Provisional PatentApplication Ser. No. 61/892,126,filed Oct. 17, 2013, entitled METHODSFOR PRODUCING ALKYL HYDROXYALKANOATES, all of which are herebyincorporated by reference in their entirety.

TECHNICAL FIELD

The present disclosure generally relates to methods and systems forproducing alkyl hydroxyalkanoates from hydroxy alkanoate recoverybottoms.

BACKGROUND

During the production and purification process of a hydroxycarboxylicacid, for example lactic acid, the hydroxycarboxylic acid is evaporatedor distilled from less-volatile compounds present in a partiallypurified fermentation broth. These less-volatile components, whichcontain significant amounts of hydroxycarboxylic acid in the form ofoligomers of hydroxycarboxylic acid and saccharide esters, are purgedout of the system as waste, which incurs a significant yield loss, aswell as solid waste disposal costs. Thus, it is desirable to turn suchwaste streams into something having economic benefit.

SUMMARY

Provided herein are methods for producing an alkyl hydroxyalkanoate,comprising obtaining a hydroxyalkanoate containing composition,comprising at least 40 percent by weight hydroxyalkanoate equivalents,less than 45 percent by weight free hydroxyalkanoates, at least 1percent by weight saccharide equivalents, and less than 15 percent byweight water; mixing a mono-alcohol in a molar ratio of from about 1.1to 1.0 to about 10.0 to 1.0 of mono-alcohol to hydroxyalkanoateequivalents present in the hydroxyalkanoate containing composition toobtain a first mixture; heating the first mixture in the presence of acatalyst to form a reaction product; and distilling the reaction productand recovering an alkyl hydroxyalkanoate fraction comprising at least 90percent by weight alkyl hydroxyalkanoate, less than 1 percent by weighthydroxyalkanoic acid, less than 1 percent by weight water; and less than0.5 percent by weight saccharide equivalents.

In the above embodiments, the hydroxyalkanoate typically comprises analpha-, beta-, or gamma- hydroxyalkanoate, for example2-hydroxypropionic acid (i.e., lactic acid) or 3-hydroxypropionic acid,preferably 2-hydroxypropionic acid. Typically, the mono-alcoholcomprises methanol, ethanol, propanol, or butanol (for example, methanolor ethanol, and preferably ethanol). Preferably, the alkylhydroxyalkanoate comprises methyl, ethyl, propyl, or butylhydroxypropionate, more preferably, ethyl lactate or ethyl3-hydroxypropionate.

FIGURES

FIGS. 1 and 2 illustrate an exemplary flow diagram for methods ofproducing ethyl lactate from lactic acid recovery bottoms.

DETAILED DESCRIPTION

“Free hydroxyalkanoate” is measured and determined using similar methodsas those described for analyzing and determining free acidity in Holten,C. H. Lactic Acid—Properties and Chemistry of Lactic Acid andDerivatives, Verlag Chemie (1971): pp. 199-203. An example calculationof free hydroxyalkanaote (i.e., free hydroxyproprionate) is set forth inthe examples below. Free hydroxyalkanoate is indicative of the monomeric2, 3, 4, and 5 carbon hydroxyalkanoic acid (i.e., hydroxycarboxylicacid), monomeric 2, 3, 4, and 5 carbon hydroxyalkanoate salts, andcombinations thereof, but not hydroxyalkanoate esters in a materialbeing measured.

“Free hydroxypropionate” is indicative of the monomeric 3 carbonhydroxypropionic acid, monomeric 3 carbon hydroxypropionate salts, andcombinations thereof, but not hydroxypropionate esters in a materialbeing measured. It is measured based on the method described for freehydroxyalkanaote.

“Hydroxyalkanoate containing composition” is defined as a mixture ofoligomers and esters of hydroxyalkanoate, for example esters withsaccharides, with optionally monomeric hydroxyalkanoates, and water. Itis typically derived from hydroxycarboxylic acid recovery bottomstreams, but may come from other sources as well.

“Hydroxyalkanoate equivalents” is measured and determined using similarmethods as those described for analyzing and determining total lactic(adjusted to account for all esters and expressed as free hydroxalkanoicacid basis) in Holten, C. H. Lactic Acid—Properties and Chemistry ofLactic Acid and Derivatives, Verlag Chemie (1971): pp. 199-203. Theesters of hydroxyalkanoate with themselves and saccharides will behydrolyzed in a similar manner to enable ready calculation ofhydroxyalkanoate equivalents. An example calculation of hydroxyalkanoateequivalents (e.g., hydroxypropionate equivalents) is set forth in theexamples below. Hydroxyalkanoate equivalents is indicative of themonomeric equivalents in the hydroxyalkanoate containing compositionwhether in the form of monomers, oligomers, and/or esters with othercompounds such as saccharides. For example, a dimeric hydroxyalkanoatecontains two hydroxyalkanoate equivalents. As another example, atrimeric hydroxyalkanoate contains three hydroxyalkanoate equivalents.As another example, a saccharide esterified with one hydroxyalkanoatecontains one hydroxyalkanoate equivalent, and a saccharide esterifiedwith two hydroxyalkanoate groups contains two hydroxyalkanoateequivalents.

“Hydroxypropionate containing composition” is defined as a mixture ofoligomers and esters of hydroxypropionate, for example esters withsaccharides, with optionally monomeric hydroxypropionates and water. Itis typically derived from lactic acid or 3-hydroxypropionic (3-HP)recovery bottom streams, but may come from other sources as well.

“Hydroxypropionate equivalents” is defined as a measure of the monomericequivalents in the hydroxypropionate containing composition whether inthe form of monomers, oligomers, and/or esters with other compounds suchas saccharides. For example, a dimeric hydroxypropionate contains twohydroxypropionate equivalents. As another example, a trimerichydroxypropionate contains three hydroxypropionate equivalents. Asanother example, a saccharide esterified with one hydroxypropionatecontains one hydroxypropionate equivalent, and a saccharide esterifiedwith two hydroxypropionate groups contains two hydroxyalkanoateequivalents. It is measured based on the method described forhydroxyalkanaote equivalents.

“Overall recovery” is defined as the moles of alkyl hydroxyalkanoaterecovered at the end of the process divided by the moles ofhydroxyalkanoate equivalents in the hydroxyalkanoate containingcomposition, multiplied by one hundred.

“Percent recovery” is defined as the moles of alkyl hydroxyalkanoaterecovered at the end of the process divided by the moles of alkylhydroxyalkanoate in the reaction product, multiplied by one hundred.

“Percent yield” is defined as the moles of alkyl hydroxyalkanoate in thereaction product divided by the moles of hydroxyalkanoate equivalents inthe hydroxyalkanoate containing composition, multiplied by one hundred.

“Recovery bottom” is defined as the purge fraction remaining after therecovery of prime monomeric hydroxycarboxylic acids, lactic acid, or3-HP acid by distillation or evaporation (or other recovery methodsknown to one of skill in the art).

“Saccharide equivalents” is defined as a measure of the monomericequivalents of saccharides whether in the form of monosaccharides,disaccharides, oligosaccharides, and/or esters with other compounds,such as hydroxycarboxylic acid. For example, a monosaccharide esterifiedwith one or more hydroxycarboxylic acids contains one saccharideequivalents. A disaccharide esterified with one or morehydroxycarboxylic acids contains two saccharide equivalents. As anotherexample, a sugar alcohol consists of one saccharide equivalent.

Producing Alkyl Hydroxyalkanoate From Hydroxycarboxylic Acid RecoveryBottoms

In one preferred embodiment, the method comprises obtaining ahydroxycarboxylic acid recovery bottom, such as the recovery bottomsobtainable from a plant manufacturing three carbon or four carbonhydroxycarboxylic acids using an evaporative or distillation-basedrecovery system, combining a C1 to C6 mono-alcohol with thehydroxycarboxylic acid recovery bottom to obtain a first mixture,heating the first mixture, optionally in the presence of a catalyst, toform a reaction product, distilling the reaction product and recoveringan alkyl hydroxyalkanoate fraction.

In one aspect of this embodiment, the hydroxycarboxylic acid recoverybottom comprises at least 40 percent (%) by weight hydroxyalkanoateequivalents, less than 5% by weight free hydroxyalkanoates, at least 1%by weight saccharide equivalents, and less than 5% by weight water.

In another more typical aspect, the hydroxycarboxylic acid recoverybottom comprises at least 40% by weight hydroxyalkanoate equivalents(for example, at least 50%, at least 60%, at least 70%, or at least 80%by weight), greater than 0% and less than 45% by weight freehydroxyalkanoates (for example, greater than 1% and less than 40%,greater than 10% and less than 40%, or greater than 10% and less than30%), at least 1% by weight saccharide equivalents, and less than 15% byweight water (for example less than 12%, less than 10%, less than 8%, orless than 5% by weight water). In one aspect, the hydroxyalkanoate maybe hydroxypropionate, and preferably lactic acid or 3-hydroxypropionicacid.

The saccharide is typically a reducing sugar, for example, glucose,maltose, isomaltose, or combinations thereof, and may also include sugaralcohols, for example, polyols such as arabitol, glycerol, orcombinations thereof.

The recovered alkyl hydroxyalkanoate fraction in this embodimentcomprises at least 90% by weight alkyl hydroxyalkanoate, less than 1% byweight hydroxycarboxylic acid, less than 1% by weight water, and lessthan 0.5% by weight saccharide equivalents. In one aspect, the alkylhydroxyalkanoate is alkyl hydroxypropionate, and preferably ethyllactate.

Producing Alkyl Hydroxyalkanoate From a Hydroxyalkanoate ContainingComposition

In another embodiment, the method comprises a first step of obtaining ahydroxyalkanoate containing composition. In preferred aspects, thehydroxyalkanoate containing composition is derived from recoverybottoms.

Hydroxyalkanoate Containing Composition

In one aspect, the hydroxyalkanoate containing composition comprises atleast 40 percent (%) by weight of hydroxyalkanoate equivalents, lessthan 5% by weight free hydroxyalkanoates, at least 1% by weightsaccharide equivalents, and less than 5% by weight water.

In another aspect, the hydroxyalkanoate containing composition of thepresent invention comprises at least 40 percent (%) by weight ofhydroxyalkanoate equivalents, greater than 0% and less than 45% byweight free hydroxyalkanoates, at least 1% by weight saccharideequivalents, and less than 15% by weight water.

(i) Hydroxyalkanoate Equivalent & Free Hydroxyalkanoate

The hydroxyalkanoate equivalents present in the hydroxyalkanoatecontaining composition makes up at least 40% by weight of the overallhydroxyalkanoate containing composition. For example, thehydroxyalkanoate containing composition may comprise at least 50% byweight hydroxyalkanoate equivalents, at least 60% by weighthydroxyalkanoate equivalents, at least 70% by weight hydroxyalkanoateequivalents, or at least 80% by weight hydroxyalkanoate equivalents.

The free hydroxyalkanoate present in the hydroxyalkanoate containingcomposition makes up greater than 0% and less than 45% by weight of theoverall hydroxyalkanoate composition. For example, the hydroxyalkanoatecontaining composition may comprise less than 40% by weight freehydroxyalkanaote, less than 35% by weight free hydroxyalkanaote, lessthan 30% by weight free hydroxyalkanaote, less than 25% by weight freehydroxyalkanaote, and in some aspects less than 5% by weight of theoverall hydroxyalkanoate composition. In other aspects, thehydroxyalkanoate containing composition comprises less than 3% by weightof free hydroxyalkanoate, less than 2% by weight of freehydroxyalkanoate, or less than 1% by weight of free hydroxyalkanoate.Yet in other aspects, the hydroxyalkanaote containing compositioncomprises at least 0.1% by weight of free hydroxyalkanoate, at least 1%by weight free hydroxyalkanoate, at least 5% by weight freehydroxyalkanoate, at least 10% by weight free hydroxyalkanoate, at least15% by weight free hydroxyalkanoate, or at least 20% by weight freehydroxyalkanoate.

In particularly preferred aspects, the amount of free hydroxyalkanaotepresent in the hydroxyalkanaoate containing composition is greater than1% and less than 40, and more preferably greater than 10% and less than40, and even more preferably greater than 10% and less than 30%. Withoutbeing bound by any theory, it is believed that increasing the amount offree hydroxyalkanoate above 1% may enhance theesterification/transesterification reaction.

The hydroxyalkanoate typically comprises an alpha-, beta-, orgamma-hydroxyalkanoate, for example 2-hydroxypropionic acid (i.e.,lactic acid) or 3-hydroxypropionic acid, and preferably2-hydroxypropionic acid.

(ii) Saccharide Equivalents

The saccharide equivalents present in the hydroxyalkanoate containingcomposition make up at least 1% by weight of the overallhydroxyalkanoate containing composition. For example, in some aspects,the saccharide equivalents make up at least 2% by weight of the overallhydroxyalkanoate containing composition, at least 3% by weight of theoverall hydroxyalkanoate containing composition, and more preferably atleast 5% by weight of the overall hydroxyalkanoate containingcomposition.

The saccharide is typically a reducing sugar, for example, glucose,maltose, isomaltose, or combinations thereof, and may also include sugaralcohols, for example, polyols such as arabitol, glycerol, orcombinations thereof.

(iii) Water

The water present in the hydroxyalkanoate containing composition makesup less than 15% by weight of the overall hydroxyalkanoate composition.For example, in some aspects, the hydroxyalkanoate containingcomposition comprises less than 12% by weight water, less than 10% byweight water, less than 8% by weight water, 3% by weight water, lessthan 2% by weight water, or preferably less than 1% by weight water.

Reacting the Hydroxyalkanoate Composition with Mono-Alcohol

For all embodiments, the mono-alcohol is typically combined with thehydroxyalkanoate containing composition. The mono-alcohol is added in amolar ratio ranging typically from 1.1 to 1.0 to 10.0 to 1.0 (forexample from 1:1 to 5:1, from 1:1 to 3:1) of mono-alcohol tohydroxyalkanoate equivalents present in the hydroxyalkanoate containingcomposition. The resultant mixture of mono-alcohol and thehydroxyalkanoate containing composition is a first mixture.

Typically, the mono-alcohol comprises methanol, ethanol, propanol, orbutanol (for example, methanol or ethanol, and preferably ethanol).

The First Mixture

For all embodiments, the first mixture is heated to form a reactionproduct. The first mixture is typically heated to a temperature rangingfrom 50 degrees Celsius (° C.) to 110° C. In alternatives, the firstmixture may be heated to a temperature ranging from 50° C. to 300° C.,for example from 50° C. to 275° C., from 50° C. to 250° C., or from 50°C. to 200° C. In certain aspects, the first mixture is heated to atemperature from the reflux temperature of the first mixture at a givenreaction pressure to 20° C. below the reflux temperature, for examplefrom the reflux temperature of the first mixture at a given reactionpressure to 10° C. below the reflux temperature, or from the refluxtemperature of the first mixture at a given reaction pressure to 5° C.below the reflux temperature of the first mixture at the given reactionpressure.

The pressure of the first mixture during the heating step typicallyranges from 0 PSIG (i.e., 1 atm) to 125 PSIG, and more preferably 50PSIG to 125 PSIG. In alternatives, the pressure of the first mixtureduring the heating step may range from 1 atm. to 100 atm, morepreferably from 5 atm. to 75 atm., and even more preferably from 10 atm.to 50 atm.

Optionally, a catalyst may be used to assist in the formation of thereaction product during the heating step. If a catalyst is used,typically the catalyst is an acid catalyst. More specifically, thecatalyst may be a solid acid catalyst, a Bronsted acid catalyst, a Lewisacid catalyst, or combinations thereof.

In a preferred aspect, the catalyst comprises sulfuric acid, and theinitial amount of catalyst present ranges from 0.01 to 5% by weight ofthe hydroxyalkanoate containing composition in the first mixture, andmore preferably ranges from 0.1 to 3% by weight of the hydroxyalkanoatecontaining composition, and even more preferably ranges from 0.5 to 2%by weight of the hydroxyalkanoate containing composition.

An alternative to using a catalyst is to run the reaction in the absenceof a catalyst. Without being bound by theory, it is believed that undersuch conditions the reaction proceeds as an autocatalyzed reaction,wherein the acid groups in the hydroxyalkanoate (e.g., lactic acid)composition are sufficient to catalyze the reaction. A particularadvantage of this alternative aspect is that it significantly reducesthe alkali needed for neutralization (optional neutralizing stepdiscussed below) prior to distillation, and also reduces the waterintroduced by the aqueous alkali, as well as that formed duringneutralization. In this alternative aspect, however, it may he necessaryto run the reaction at a higher temperature and pressure (when comparedto catalyzed reactions) to achieve the desired yields in a reasonableperiod of time.

Optional Neutralizing/pH Adjustment Step

For all embodiments, an optional neutralizing/pH adjustment step may becarried out before distillation. In this step, the pH of the acidcatalyst and any free organic acids that remain in the reaction productmay be adjusted using a concentrated base solution to a targeted pHvalue typically ranging from 3 to 7.5, for example from 4 to 6.5, orfrom 4 to 6. In some instances, it may be desirable to obtain a pH from6.5 to 7.5.

Optional High Boiling Solvent Addition Step

For all embodiments, optionally, a high boiling solvent, for example butnot limited to glycerol, may be added to the reaction product (after thereaction to form the first mixture)) before the distillation step, tomaintain the first mixture in a fluid state during the distillation.

Distilling the Reaction Product

For all embodiments, the reaction product typically is subsequentlydistilled. Specifically, the reaction product is distilled to recover analkyl hydroxyalkanoate fraction. In a typical aspect, the alkylhydroxyalkanoate fraction comprises at least 90% by weight alkylhydroxyalkanoate, less than 1% by weight hydroxyalkanoic acid, less than1% by weight water, and less than 0.5% by weight saccharide equivalents;and the saccharide equivalents in the alkyl hydroxyalkanoate fraction isless than 0.1% by weight or even less than 0.05% by weight.

Preferably, the alkyl hydroxyalkanoate comprises methyl, ethyl, propyl,or butyl hydroxypropionate, and more preferably ethyl lactate or ethyl3-HP.

In a first aspect, the distillation step comprises separating thereaction product into a first fraction enriched in the mono-alcohol andwater, and a second fraction, which may be in the form of distillatebottoms, enriched in the alkyl hydroxyalkanoate, wherein the alkylhydroxyalkanoate fraction is recovered from the second fraction. Theseparation into the first fraction and the second fraction may becarried out using fractional distillation.

In a second aspect, the distillation step comprises a first step toprovide a first fraction enriched in water and mono-alcohol and a secondfraction, which may be in the form of distillate bottoms, enriched inalkyl hydroxyalkanoate and saccharide, and a second step to fractionatethe second fraction into a saccharide enriched fraction and the alkylhydroxyalkanoate fraction. This second step may be carried out utilizingan evaporator. The evaporator may be a forced circulation evaporator, aboiling tube evaporator (“BTE”), a wiped film evaporator (“WFE”), arising film evaporator, or a climbing evaporator.

In a third aspect, the distillation step comprises a first step toprovide a first fraction enriched in water, mono-alcohol, and alkylhydroxyalkanoate, and a second fraction, which may be in the form ofdistillate bottoms, enriched in saccharide. Further, this embodimentcomprises a second step to fractionate the first fraction into a waterand mono-alcohol enriched fraction and the alkyl hydroxyalkanoatefraction. This second step may be carried out utilizing fractionaldistillation or an evaporator. The evaporator may be a forcedcirculation evaporator, a boiling tube evaporator, a wiped filmevaporator, a rising film evaporator, or a climbing evaporator.

In the distillation processes described above, a reduced pressuretypically below atmospheric pressure is used to recover the alkylhydroxyalkanoate fraction. In certain aspects, the pressure of thedistillation step may range from 0.1 torr to 750 torr, 0.1 torr to 200torr, 0.1 torr to 100 torr, and more specifically 0.5 torr to 100 torr.

It is desirable to carry out the distillation process under high vacuumconditions to minimize contact time and temperature, which consequentlyminimizes undesirable interfering reactions. In the various aspects, themaximum temperature in which to operate distillation is typically 160°C. at atmospheric pressure, which consequently minimizes thedistillation of higher molecular weight organic acid esters, forexample, esters of succinic acid.

In certain aspects, the reaction product typically has a compositioncomprising less than 3% by weight of high molecular weight organic acidesters, and more preferably less than 2% by weight percent of highmolecular weight organic acid esters, and even more preferably less than1% by weight of high molecular weight organic acid esters as itprogresses through the series of distillation steps.

Percent Yield & Percent Recovery

For all embodiments, the percent yield is typically greater than 50%,for example, greater than 60%, greater than 70%, greater than 80%,greater than 90%, and more preferably greater than 95%. The percentrecovery is typically greater than 50%, for example, greater than 60%,greater than 70%, greater than 80%, greater than 90%, and, morepreferably greater than 95%.

Methods

The following methods described further below are used in the variousexamples and are presented to illustrate the present invention and toassist one of ordinary skill in making and using the same. The methodsare not intended in any way to otherwise limit the scope of theinvention.

Method for Calculating Free Alkanoates and Alkanoate Equivalents

The free hydroxyalkanoate and total hydroxyalkanaote content inhydroxyalkanoate containing compositions is determined by a titrationmethod similar to the method described in the Holten reference above.“Bound” hydroxyalkanoate is the hydroxyalkanoate that is in the form ofesters and is calculated as shown below. Hydroxyalkanoate equivalentscan then be calculated from the free and bound. hydroxyalkanoates.

Free hydroxyalkanoate=J% by weight (J is similar to the free acidity,i.e., a, in the Holten reference)

Total hydroxyalkanoate=K% by weight (K is similar to the total lacticacid, i.e., a+b, in the Holten reference)

Bound hydroxyalkanoate=(K−J)% by weight

Hydroxyalkanoate Equivalents=J+[(K−J)×C]% (where “C” for 3 carbonhydroxyalkanoates is 90/72; where “C” for 4 carbon hydroxyalkanoates is104/86; where “C” for 5 carbon hydroxyalkanoates 118/100)

Ultra Performance Liquid Chromatography (UPLC) Method for the Analysisof Ethyl Lactate

This method is used to analyze the content of ethyl lactate in reactionmixtures. The UPLC method consists of the following steps:

Sample prep: An aliquot of approximately 128 mg (+5 mg) of sample isadded to a graduated 15 mL polypropylene centrifuge tube, using avolumetric pipette, with 1 mL internal standard (I.S.). The internalstandard is methyl lactate in acetonitrile at a concentration of 55mg/ml. The sample is brought to the 5 mL mark with acetonitrile, cappedtightly, and vortexed for 30 seconds followed by sonication for 3minutes. After sonication, the sample is centrifuged for 3 minutes at5000 RPM using a microcentrifuge, then 200 microliters (μL) of thesupernatant is transferred to a limited volume LC vial and subject toUPLC-UV (210 nm) analysis, as explained in Step (2) below. The finalconcentration of the internal standard in the sample is approximately 11mg/mL. The pressure used for this method ranges from 8000 to 10000 psi.

Chromatographic separation: For this step, a Waters UPLC is used alongwith Waters Acquity HSS T3 C18, 2.1 mm×100 mm, 1.8 μm analytical column.The column is maintained at 40° C. A mobile phase gradient is used wheremobile phase A is 0.1% formic acid and mobile phase B is acetonitrile,the phase gradient is outlined in Table 1. The retention time for ethyllactate is 4.67 minutes, and the retention time for methyl lactate (IS)is 3.02 minutes. Injection volume of 1 μL, is used and the detection isdone with a Waters Acquity, PDA detector.

TABLE 1 Time Flow Rate (min) (mL/min) % A % B Initial 0.52 100.0 0.01.00 0.52 100.0 0.0 3.80 0.52 92.5 7.5 4.70 0.52 92.5 7.5 5.20 0.52 90.010.0 5.60 0.57 5.0 95.0 7.00 0.62 5.0 95.0 7.10 0.62 100.0 0.0 8.70 0.62100.0 0.0 9.00 0.52 100.0 0.0Ultra High Performance Liquid Chromatography (UHPLC) Method for theAnalysis of Ethyl 3-Hydroxypriopionate:

This method is used to analyze the content of ethyl 3-hydroxypropionatein reaction mixtures. Approximately 1 gram of sample is weighed into a50 mL volumetric flask. The analyte is extracted with 50 ml acetonitrileby sonication for 5 minutes. The solution is transferred to a 50 mLcentrifuge tube and centrifuged at 3000 rpm for 3 minutes. Thesupernatant is removed for analysis via UHPLC as follows:

Chromatographic separation: 1 μL of the extraction solution is injectedonto either a Waters Acquity UPLC or Agilent 1290 UHPLC. Separation ofanalytes is performed on a Waters Acquity HSS T3 C18, 2.1 mm×100 mm, 1.8μm analytical column. The column is maintained at 30° C. A mobile phasegradient is used where mobile phase A is 0.1% formic acid and mobilephase B is acetonitrile, the phase gradient is outlined in Table 2. Theretention time for ethyl 3-HP is 2.2 minutes. Quantification of ethyl3-HP is performed by applying the peak area of the test sample directlyto areas for a set of standards measured by UV at 210 nm.

TABLE 2 Time Flow Rate (min) (mL/min) % A % B Initial 0.6 97.0 3.0 0.50.6 97.0 3.0 2.5 0.6 82.0 18.0 3.0 0.6 5.0 95.0 3.5 0.6 5.0 95.0 4.0 0.697.0 3.0 5.5 0.6 97.0 3.0GC Method 1: Measuring Ethyl Lactate Concentration in DistilledFractions Using GC-FID Method:

An Agilent 7890 Gas Chromatograph with a flame ionization detector isused to measure the purity of ethyl lactate in the distilled samples. AHewlett Packard HP-5 column (length=25 m, i.d.=0.2 mm, film=0.5 mm) isused. The run profile is: 50° C. initial, hold 4.4 min, 30° C./min to200° C., hold 2.6 min, and then 30° C./min to 250° C., hold 2.6 min. Therun time is 16.27 minutes. The inlet temperature is 250° C., the carriergas is hydrogen, with a flow rate of 0.5 mL/min, and detectortemperature of 300° C. The FID makeup is: Nitrogen (30 mL/min); FIDFuel: Hydrogen (40 mL/min); FID Oxidizer: Air (350 mL/min).

100 μL of a distillate sample is placed in a culture tube, and 5 mL ofacetonitrile (GC grade) is added. The tube is capped and mixedthoroughly. 1.5 mL of this solution is transferred to a 2 mL GC vial,which is sealed by crimping on a Teflon-lined cap. Injection Volume=1.0μL. The concentration of ethyl lactate is based on integration of theethyl lactate peak in the chromatogram relative to all the other peaks,while ignoring the solvent peak (acetonitrile). The retention time forethyl lactate is 7.1 min.

It shall be understood that this method is the preferred method formeasuring ethyl lactate concentrations less than about 95% and is themethod used in the relevant claim recitations.

GC Method 2: GC Analysis of Ethyl Lactate and Ethanol in ReactionMixtures

The GC instrument is an Agilent 7890 Gas Chromatograph withsplit/splitless injector and flame ionization detector. The column is anAgilent HP-5 column (length=25 m, i.d.=0.2 mm, film=0.5 μm). Initialoven temperature was 50° C., held for 3.0 min, then a 15° C./min ramp upto 325° C., and held there for 8.67 min, for a total run time of 30 min.Inlet Temperature at 275° C., with Hydrogen as the carrier gas at aconstant flow of 0.5 mL/min. The FID detector temperature was 275° C.,with Hydrogen (40 mL/min) as the fuel.

100 mg of the test material was diluted with 5 mL of GC gradeAcetonitrile in a culture tube. The tube was capped and mixed thoroughlyby sonication. Filtered 1.5 mL of the solution through a 0.2 μm filter,and transferred to a GC vial with a Teflon-lined cap. Sample injectionvolume was 1.0 μL.

The retention times of ethanol and ethyl lactate were approximately 2.16min and 6.56 min respectively. The concentrations of ethanol and ethyllactate in the reaction mixtures were determined based on peakintensities compared with individual standard curves generated with highpurity ethanol and ethyl lactate.

It shall be understood that this method is used to determine ethyllactate concentration in certain examples, but is not the preferredmethod of determining ethyl lactate.

GC Method 3: GC Analysis of High Concentrations of Ethyl Lactate

The GC instrument, column, program etc. are identical to GC Method 2above, The only difference was the sample was injected into the GCwithout dilution in a solvent. Approximately 1 mL of sample was placedin a GC vial containing a Teflon-lined cap, and 0.2 μL was injected. The% area of ethyl lactate relative to all the other components, minuspeaks from the solvent, was reported as the purity of ethyl lactate. Itshall be understood that this method is the preferred method formeasuring ethyl lactate concentrations greater than and equal 95% and isthe method used in the relevant claim recitations.

Method for Determining APHA Color

APHA color, also referred to as the Hazen scale, and more appropriatelyas the Platinum Cobalt(Pt/Co) scale, is a color standard named for theAmerican Public Health Association and defined by ASTM D1209.

EXAMPLES

The following examples are presented to illustrate the present inventionand to assist one of ordinary skill in making and using the same. Theexamples are not intended in any way to otherwise limit the scope of theinvention.

Note, for all tables that refer to moisture percent it shall beunderstood that moisture percent refers to water content/percent.

Example 1 Production of Ethyl Lactate Using Recovery Bottoms

50.42 grams of recovery bottom sample from a lactic acid process, havinga composition as detailed in Table 3, is mixed with 50.42 grams ofethanol (200 proof). To this first mixture, 1% by weight relative to therecovery bottom of 98% sulfuric acid is added as the catalyst to formthe reaction mixture. The reaction mixture is constantly stirred and isheated to a temperature of 78-80° C. and is carried out at atmosphericpressure. The reaction mixture is held at this temperature for 5 hours,after which the reaction mixture contains 24.72 grams of ethyl lactate.This equates to a percent yield of 52.5%. The ethyl lactate in thereaction mixture is measured using the UPLC method.

TABLE 3 Compound Weight Percent (wt %) Lactic Acid Equivalents 71.23 wt% (i.e., lactate equivalents) Free lactic acid <1 wt % (i.e., freelactate) Saccharide Equivalents 11.1 wt % Water <1 wt %

Example 2 Production of Ethyl Lactate Using Recovery Bottoms

52.8 grams of recovery bottom sample from a lactic acid process, havinga composition as detailed in Table 3, is mixed with 52.8 grams ofethanol (200 proof). To this first mixture, 1% by weight relative to therecovery bottom of 35% aqueous hydrochloric acid is added as thecatalyst to form the reaction mixture. The reaction mixture isconstantly stirred and is heated to a temperature of 78-80° C. and iscarried out at atmospheric pressure. The reaction mixture is held atthis temperature for 5 hours, after which the reaction mixture contains24.33 grams of ethyl lactate. This equates to a percent yield of 49.6%.The ethyl lactate in the reaction mixture is measured using the UPLCmethod.

Example 3 Production of Ethyl Lactate Using Recovery Bottoms

54.3 grams of recovery bottom sample from a lactic acid process, havinga composition as detailed in Table 3, is mixed with 54.3 grams ofethanol (200 proof). To this first mixture, 1% by weight sodiumhydroxide relative to the recovery bottom is added as the catalyst toform the reaction mixture. The reaction mixture is constantly stirredand is heated to a temperature of 78-80° C. and is carried out atatmospheric pressure. The reaction mixture is held at this temperaturefor 5 hours, after which the reaction mixture contains 5.41 grams ofethyl lactate. This equates to a percent yield of 10.7%. The ethyllactate in the reaction mixture is measured using the UPLC method.

Example 4 Production and Distillation of Ethyl Lactate Using RecoveryBottoms

125.3 grams of recovery bottoms sample from a lactic acid process,having a composition as detailed in Table 3, is mixed with 125.3 gramsof ethanol (200 proof). To this first mixture. 2% by weight relative tothe recovery bottom of 98% sulfuric acid is added as the catalyst toform the reaction mixture. The reaction mixture is constantly stirredand is heated to a temperature of 78-80° C. and is carried out atatmospheric pressure. The reaction is carried out for 10 hours at whichpoint the reaction mixture contains 86.42 grams of ethyl lactate. Thisequates to a percent yield of 73.8%. The ethyl lactate in the reactionmixture is measured using the UPLC method.

The reaction mixture is neutralized with sodium ethoxide to a pH of 7.209 grams of this neutralized reaction product is used as a feed for thedistillation process. Fractional distillation experiments are carriedout in batch scale distillation in a flask at 100 torr. Table 4 showsthe conditions under which six fractions are collected and theconcentration of ethyl lactate in each fraction is determined using theGC-FID method (GC Method 1), as described above. The total amount ofethyl lactate recovered in these fractions equates to 100 percentrecovery by distillation. The overall yield for the process is 73.8%.Although the recovery does not appear high in certain fractions, oneskilled in the art would understand that an increased number oftheoretical stages/plates in a commercial setup will provide highpercent recovery and high purity. For example, typically greater than 80percent recovery, typically 90 percent recovery, and in some instancesgreater than 92 percent recovery; and, with greater than 90% purity, forexample, 95% purity, typically 98% purity, in some instances greaterthan 99% purity.

TABLE 4 Sample I.D. Feed Frac. 1 Frac. 2 Frac. 3 Frac. 4 Frac. 5 Frac. 6Ethyl Lactate wt in grams 57.3 0 0.5 3.8 13.1 24.9 15.1 feed and eachfraction Ethyl Lactate Purity wt % 27.40 0.00 3.20 11.50 44.70 80.4076.40 in feed and each fraction Temperature ° C. — 34 39 46 108 136 160Pressure (absolute) Torr 100 100 100 100 100 100

Example 5 Production and Distillation of Ethyl Lactate Using RecoveryBottoms

Experiments may be carried out using a 50 L jacketed reactor. First,17.7 kilograms ethanol is added to the reactor and heated to 50° C. bypassing hot water through the reactor jacket. The hot water iscirculated using a hot water bath. 17.7 kilograms of recovery bottomsample from a lactic acid process, the composition of which is specifiedin Table 3, is preheated to 78-80° C. and added to the reactor. To thisfirst mixture, 2% by weight relative to the recovery bottom of 98%sulfuric acid is added as the catalyst. The reaction is carried out for6 hours at 78-80° C. and at atmospheric pressure to thrift the reactionproduct. A sample of the reaction mixture is taken from the reactor andethyl lactate concentration is determined using the UPLC method. Thereaction mixture has 12.94 kilograms of ethyl lactate which equates to apercent yield of 78.34%. The synthesized ethyl lactate is subsequentlyneutralized using sodium ethoxide and the neutralized reaction mixtureis used as a feed for the distillation.

Distillation experiments are carried out with laboratory pilot scalerotovap (Buchi Rotovapor R-153) with a provision for continuous feedusing 39.64 kilograms of neutralized reaction product. This setup hasthe capability to measure the inline vapor temperature along with thebath temperature. Three different distillate fractions are collected andthe concentration of ethyl lactate in each fraction determined using theGC-FID method (GC Method 1), as illustrated in Table 5. The firstfraction is ethanol with 0 wt % ethyl lactate, the second fractioncontains 58.63 wt % of ethyl lactate, and the third fraction contains96.88 wt % ethyl lactate concentration with 0.9 wt % moisture and anacid value of 750 ppm. The percent recovery is 67.5% and the overallrecovery is 52.8%.

As demonstrated in Table 5, reduced pressures, for example below 30 Torr(Fraction 3), improve the purity of the ethyl lactate.

TABLE 5 Sample I.D. Feed Frac. 1 Frac. 2 Frac. 3 Ethyl Lactate purity infeed wt % 30.10 — 58.63 96.88 and each fraction Ethyl Lactate wt in feedand Kg 11.93 — 4.46 3.6 each fraction Bath Temp. ° C. — 62 75 97 VaporTemp. ° C. — 47 62 57 Pressure (absolute) Torr — 90 32 17

Further, distillation is carried out of the second fraction of the firstdistilled product which contains 58.63 wt % of ethyl lactateconcentration. In the second distillation, again three fractions arecollected, and are summarized in Table 6.

TABLE 6 Sample I.D. Feed Frac. 1 Frac. 2 Frac. 3 Ethyl lactate purity infeed and each fraction wt % 58.63 — 54.22 99.68 Bath Temp, ° C. — 32 7080 Vapor Temp. ° C. — 32 65 72 Pressure (absolute) Torr — 42 42 42

As illustrated in Table 6, the third fraction contains 99.68 wt % ethyllactate concentration with 0.07 wt % moisture and an acid value of 550ppm, demonstrating that a series of distillation steps of a specificfraction can further improve ethyl lactate purity.

Example 6 Effect of pH on Ethyl Lactate Recovery

Reaction is carried out in a 2 L round bottom glass flask by mixinglactic acid solids (BTE bottoms) and ethanol. The round bottom flask isattached to a vertical glass condenser which is cooled with 5-7° C.water. The total reaction mixture weighs approximately 1500 gm with amass ratio of 60:40 ethanol to lactic acid solids. The added ethanol isin molar excess to drive the reaction towards formation of ethyllactate. The mixture is heated to 72-75° C. At this point 1.54% of 93%sulfuric acid is added to the reaction mix and the reaction is furtherheated to 80-83° C. and maintained at this temperature for 8 hours. Thereaction is cooled to 23-25° C. and is divided into 3 aliquots eachweighing approximately 300 grams. One of these aliquots is neutralizedwith 50% sodium hydroxide to pH 4, second aliquot is neutralized to pH 5with 50% sodium hydroxide and the third aliquot is was neutralized to pH6 with 50% sodium hydroxide

Each of these neutralized aliquots is processed in a glass distillationset-up in a batch mode to recover the volatile components namelyethanol, water and ethyl lactate as an overhead distillate. The ethyllactate in the distillate and bottom residue is measured using GC Method2. The distillation conditions are in Table 7.

TABLE 7 Tray or packing None Max Reboiler Temp (° C.) 137.3-145   MaxVacuum (Torr) 7 Condenser Temp (° C.) 2 Vapor Temp (° C.) 66.9-67.2

The results of the distillation trial are tabulated in Table 8, Table 9,and Table 10.

TABLE 8 Residue Distillate Cold Trap pH 6 Feed Composition CompositionComposition Composition Component % (grams) % (grams) % (grams) %(grams) % Recovered Total Mass N/A 314.19 N/A 90.19 N/A 215.16 N/A 097.19 Ethyl Lactate 31.68 99.53 5.65 5.10 42.12 90.63 0.00 0.00 96.17

TABLE 9 Residue Distillate Cold Trap pH 5 Feed Composition CompositionComposition Composition Component % (grams) % (grams) % (grams) %(grams) % Recovered Total Mass N/A 311.75 N/A 94.95 N/A 214.98 N/A 0.3499.53 Ethyl Lactate 30.62 95.46 2.88 2.73 42.22 90.76 1.20 0.00 97.94

TABLE 10 Feed Residue Distillate Cold Trap pH 4 Composition CompositionComposition Composition Component % (grams) % (grams) % (grams) %(grams) % Recovered Total Mass N/A 301.32 N/A 86.73 N/A 211.96 N/A 0.5699.31 Ethyl Lactate 34.02 102.50 2.32 2.01 45.53 96.51 3.44 0.02 96.14

As illustrated in the tables, ethyl lactate recovery remains high at pHranges of 4, 5, and 6. Thus, as stated above, a neutralization to a pHof 7 is not required which can provide cost savings (as it minimizes theamount of base used and process time necessary to raise the pH) andminimizes the water content.

Example 7 Distillation Configuration #1

Refer to FIG. 1 for an illustration of the block diagram for thisconfiguration. First, a stirred tank jacketed reactor or a tubular flowreactor is used to react lactic acid recovery bottoms and ethanol in thepresence of a sulfuric acid catalyst. Sodium hydroxide is added to thereactant before entering a first distillation step. The firstdistillation is a wiped film evaporator unit in which the volatilecomponents comprising ethanol, water and ethyl lactate are recovered asa distillate. The non-volatile components are taken out as the bottomresidue stream. The distillate from the first distillation step enters asecond distillation step. The second distillation step is a fractionaldistillation using a packed or tray column, and preferably a packedcolumn. In this set-up, the ethanol-water mix is collected as adistillate, while the product of interest, ethyl lactate, is collectedas the bottom product. Considering that ethyl lactate forms the bottomsstream, it is challenging to achieve high purity ethyl lactate becauseminor impurities such as color bodies remain in the bottoms stream. Thisissue may be overcome by including an additional distillation unit inwhich the bottom product from the second distillation step is fed to anadditional distillation unit and ethyl lactate is recovered as adistillate product.

Example 8 Sample Distillation Configuration #2

Refer to FIG. 2 for an illustration of the block diagram for thisconfiguration. First, a stirred tank, jacketed reactor or a tubular flowreactor is used to react lactic acid recovery bottoms and ethanol in thepresence of a sulfuric acid catalyst. Sodium hydroxide is added to thereactant before entering a first distillation step. The firstdistillation is a fractional distillation using a packed or tray column,and preferably a hybrid column with a tray in the bottoms section andpacking in the top section of the distillation column. Ethanol and waterare taken off as the distillate, and the bottoms move on to a seconddistillation step, which utilizes a wiped film evaporator with anattached column to recover ethyl lactate as a distillate. The wiped filmevaporator acts like a reboiler and column and thus achieves a higherpurity of ethyl lactate (in the distillate) when compared againstExample 7. The advantage of this configuration is that since ethyllactate is recovered as the distillate, minor impurities such as thecolor bodies remain in the bottoms.

Whereas the ethyl lactate in Distillation Configuration 1 has a yellowcolor, three experiments utilizing Distillation Configuration 2 producedethyl lactate with APHA colors around 10 or below, as demonstrated inTable 11.

TABLE 11 Target Lot A Lot B Lot C Ethyl lactate Purity 98.39% 98.81%98.24% (%) - GC Color (APHA) 10 max 8.6 10.1 9.3

Example 9 Synthesis of Ethyl Lactate from Lactic Acid Recovery Bottoms(“BTE Bottoms”) Under Pressure With and Without a Catalyst

A high temperature oven was heated to the desired temperature (see below150, 175, 200, or 220° C.), Six 600 mL beakers were filled halfway withsilica and placed in the oven to acclimate to the temperature. Six 1″stainless steel Swagelok assemblies (part# OMA-CARLAB-003-0) werecleaned and dried. Both ends of each assembly were Teflon taped andSilver Goop® Thread Lubricant Oil-Based Swagelok (part# MS-TL-SGT) wasused around the threads on top of the Teflon tape and on the threads ofthe caps, then one end of each assembly was capped and secured.

The reaction mixture was 60:40 or 40:60 (w/w) as indicated below ofEthanol (Cargill, purity >99%) to BTE bottoms, The reaction mixture (250g) was prepared in a 250 ml bottle and allowed to mix in a sonicatoruntil the mixture was homogeneous. Then 25 grams of reaction mixture wastransferred into six 40 ml glass vials. The contents of the vials weretransferred into the six Swagelok assemblies, then capped and secured.The capacity of the assembly is approximately 50 ml. Excessivetightening was essential to ensure a proper seal at the desiredtemperature.

The beakers were carefully removed from the oven and each Swagelokassembly was wedged into its own beaker of silica so that the bottomscap was covered. The six beaker assembly combinations were then placedback in the oven. Every 45 minutes one beaker assembly combination wasremoved from the oven and the assembly was taken out of the silica tocool in front of a fan. When the assembly was cool the contents weretransferred to a 40 ml glass vial to be analyzed via GC. The moistureanalysis (Karl Fisher) and pH were also taken for each sample. BTEBottoms analysis by the titration method mentioned above had thefollowing numbers in Table 12:

TABLE 12 Free Lactate 35.95% Lactate Equivalents 79.40%

Trial 1: Oven Temperature 120° C., 60:40 (w/w) Ethanol to BTE Bottoms,50 ml glass pressure tubes, Reaction time 15 hrs: (Table 13)

TABLE 13 Yield Moisture Sample (%) (%) Rxn 1 48.6 3.56 Rxn 2 49.8 3.18

Trial 2: Oven Temperature 150 or 175° C., 1^(st) set 60:40 and 2^(nd)set 40:60 Ethanol to BTE Bottoms, Reaction Time 15 hrs: (Table 14)

TABLE 14 Yield Moisture Sample (%) pH (%) Rxn 1 60:40 150° C. 59.1 2.93.97 Rxn 2 40:60 150° C. 58.3 2.2 5.11 Rxn 3 60:40 175° C. 64.9 2.9 3.69Rxn 4 40:60 175° C. 59.1 2.4 5.48

Trial 3: Oven Temperature 200° C., 60:40 (w/w) Ethanol to BTE Bottoms:(Table 15)

TABLE 15 Yield Moisture Sample (%) pH (%) Rxn 1 45 min 6.9 2.5 2.10 Rxn2 90 min 40.1 2.6 3.19 Rxn 3 135 min 58.4 2.2 2.72 Rxn 4 180 min 69.52.3 3.98 Rxn 5 225 min 72.8 2.3 4.34 Rxn 6 270 min 73.7 2.4 4.32

Trial 4: Oven Temperature 220° C., 60:40 (w/w) Ethanol to BTE Bottoms:(Table 16)

TABLE 16 Yield Moisture Sample (%) pH (%) Rxn 1 45 min 7.0 2.5 2.34 Rxn2 90 min 29.4 2.7 3.33 Rxn 3 135 min 59.4 2.8 3.92 Rxn 4 180 min 71.12.7 4.73 Rxn 5 225 min 73.5 2.8 5.01 Rxn 6 270 min 73.2 2.8 5.48

Trial 5: Oven Temperature 200° C., 60:40 (w/w) Ethanol to BTE Bottoms,4% water addition based off of the total BTE bottoms mass: (Table 17)

TABLE 17 Yield Moisture Sample (%) pH (%) Rxn 1 45 min 2.9 — — Rxn 2 90min 19.9 — — Rxn 3 135 min 49.1 — — Rxn 4 180 min 62.5 — — Rxn 5 225 min66.9 — — Rxn 6 270 min 67.7 2.8 5.66

Trial 6: Oven Temperature 200° C., 60:40 (w/w) Ethanol to BTE Bottoms,0.2% Sulfuric acid addition based off of the total reaction mixture:(Table 18)

TABLE 18 Yield Moisture Sample (%) pH (%) Rxn 1 45 min 14.8 — — Rxn 2 90min 40.2 — — Rxn 3 135 min 58.4 — — Rxn 4 180 min 69.4 — — Rxn 5 225 min74.7 1.7 4.58 Rxn 6 270 min 74.7 1.7 5.32

Example 10 Synthesis of Ethyl Lactate from WFE Bottoms

Recovery bottoms sample from the Cargill Lactic Acid process, having acomposition as detailed in Table 19 below, is mixed with deionized waterat a 1.05 molar ratio of water to the ester bonds in the bound lacticacid. 93% sulfuric acid at 1% by weight relative to the total reactionmass is added as the catalyst to the reaction mixture. The reactionmixture is constantly stirred and heated to a temperature of 100° C.under atmospheric pressure for 8 hours. It is believed that free lacticis at least about 20%. The reaction mixture is then mixed with ethanol(Cargill. purity >99%) at the mass ratio of 70:30 of ethanol to reactionmixture. 93% sulfuric acid at 1.44% by weight relative to the totalreaction mass is added as the catalyst to the reaction mixture. Thereaction mixture is constantly stirred and heated to a temperature of80-83° C. under atmospheric pressure. The reaction mixture is held atthis temperature for 8 hours, and samples are withdrawn at 6 hr and 8 hrfor analysis. The total mass is then neutralized with 50% aqueous NaOHto a pH of 4.0 and sampled. The ethyl lactate and moisture content inthe collected samples are analyzed via GC and Karl Fisher respectively.The results of the reactions are provided in Table 20, Table 21, andTable 22.

TABLE 19 Free lactate 11.72% Lactate Equivalents 64.70%

TABLE 20 Mass (g) Reaction Step Components Rxn 1 Rxn 2 Hydrolysis WFEBottoms 350.94 351.19 Water 39.01 39.08 93% Sulfuric Acid 4.20 4.23Ester Formation Ethanol 920.03 921.07 93% Sulfuric Acid 20.26 20.46Neutralization NaOH 22.92 22.98

TABLE 21 Reaction 1 Moisture Ethyl Lactate Yield Sample (%) (% in RxnMixture) (%) 6 hr 4.07 16.65 74.3 8 hr 3.82 16.63 73.6 Neutralized 4.8215.41 68.6

TABLE 22 Reaction 2 Moisture Ethyl Lactate Yield Sample (%) (% in RxnMixture) (%) 6 hr 4.01 16.26 72.5 8 hr 3.84 17.21 76.0 Neutralized 4.8716.42 73.0

Recovery bottoms sample from the Cargill Lactic Acid process, having acomposition as detailed in Table 19 above is mixed with deionized waterat a 0.8 molar ratio of water to the ester bonds in the bound lacticacid. The rest of the reaction is procedurally identical to the abovereactions. The results of this reaction are provided in Table 23 andTable 24.

TABLE 23 Mass (g) Reaction Step Components Rxn 3 Hydrolysis WFE Bottoms352.05 Water 29.90 93% Sulfuric Acid 4.19 Ester Formation Ethanol 902.6993% Sulfuric Acid 19.89 Neutralization NaOH 22.29

TABLE 24 Reaction 3 Moisture Ethyl Lactate Yield Sample (%) (% in RxnMixture) (%) 6 hr 3.29 17.32 75.5 8 hr 3.20 17.50 75.5 Neutralized 4.6515.96 69.3

An example similar to Example 10 is carried out (utilizing the similarrecovery bottoms and reaction conditions) except deionized water is notadded resulting in a percent yield of approximately 30%, at leastdoubling the percent yield compared to when deionized water is added.This shows that in some instances increasing the free alkanoate to atleast 20% can increase the percent yield and overall recovery.Alternatively, higher temperature and higher pressure could be utilizedto obtain higher percent yield and overall recovery.

Example 11 Reaction of 3-hydroxypriopionic Acid Recovery Bottoms(“3-HPRB”) with Ethanol (“EtOH”)

Recovery bottoms from a 3-Hydroxypropionic acid (3-HP) manufacturingprocess that utilizes a distillation process tier recovering 3-HP areobtained having a composition as detailed in the Table 25 below aremixed with ethanol (200 proof) at mass ratios of 50:50, 40:60 or 30:70of 3-HPRB to ethanol. 98% sulfuric acid at 1 to 4% by weight relative tothe 3-HPRB is added as the catalyst to the reaction mixture. Thereaction mixture is constantly stirred and heated to a temperature of78-80° C. under atmospheric pressure. The reaction mixture is held atthis temperature for 6 to 14 hours, after which it is cooled to roomtemperature and analyzed by UHPLC. The composition of the resultingproduct is detailed in Table 26.

TABLE 25 Compound Weight Percent (wt %) 3-HP Equivalents 66.74 wt % Free3-HP 11.53 wt % Saccharide Equivalents   >1 wt %  Water  >0.1 wt %  

TABLE 26 Reaction Total weight of Yield of 3-HP Reaction mixture (Massratio) time (hrs) reaction mixture (g) ethyl ester (%) 3-HPRB:EtOH(50:50)-6 hr., 1% H2SO4 6 108.47 56.14 3-HPRB:EtOH (50:50)-6 hr., 2%H2SO4 6 112.95 52.97 3-HPRB:EtOH (50:50)-6 hr., 3% H2SO4 6 103.85 50.813-HPRB:EtOH (50:50)-6 hr., 4% H2SO4 6 99.62 48.38 3-HPRB:EtOH (50:50)-6Hr., 3% H2SO4 6 113.60 51.74 3-HPRB:EtOH (40:60)-6 Hr., 3% H2SO4 6112.65 60.54 3-HPRB:EtOH (30:70)-6 Hr., 3% H2SO4 6 106.73 66.753-HPRB:EtOH (30:70)-8 Hr., 3% H2SO4 8 112.37 66.34 3-HPRB:EtOH(30:70)-10 Hr., 3% H2SO4 10 122.33 67.24 3-HPRB:EtOH (30:70)-14 Hr., 3%H2SO4 14 112.44 65.12

The results in Table 26 show that no large differences in yield areobserved with an increase in catalyst concentration. Further, increasingthe ethanol content relative to the 3-HP distillation bottoms from 50:50to 70:30 increases the yield of 3-HP ethyl ester and increasing the timeof the reaction beyond 6 hours at 3-HP distillation bottoms to ethanolratio of 3:7 did not increase the yield. i.e., the reaction appears toreach equilibrium in about 6 hours

We claim:
 1. A method for producing an alkyl hydroxypropionate, themethod comprising: a) obtaining a hydroxyalkanoate containingcomposition comprising hydroxypropionate, the hydroxyalkanoatecontaining composition further comprising: (i) at least 40 percent byweight hydroxyalkanoate equivalents; (ii) less than 45 percent by weightfree hydroxyalkanoates; (iii) at least 1 percent by weight saccharideequivalents; and (iv) less than 15 percent by weight water; b) mixing amono-alcohol selected from the group consisting of C1 to C6mono-alcohols in a molar ratio of from 1.1:1 to 10.0:1 of mono-alcoholto hydroxyalkanoate equivalents present in the hydroxyalkanoatecontaining composition to obtain a first mixture; c) heating the firstmixture in the presence of a catalyst to form a reaction product; d)distilling the reaction product and recovering an alkylhydroxypropionate fraction comprising: (i) at least 90 percent by weightalkyl hydroxypropionate; (ii) less than 1 percent by weighthydroxypropionic acid; (iii) less than 1 percent by weight water; and(iv) less than 0.5 percent by weight saccharide equivalents.
 2. Themethod of claim 1, wherein step (d) comprises fractional distillation.3. The method of claim 1, wherein step (d) comprises: a first step toprovide a first fraction enriched in water, mono-alcohol, and alkylhydroxypropionate and a second fraction enriched in saccharideequivalents; and a second step to fractionate the first fraction into awater and mono-alcohol enriched fraction and the alkyl hydroxypropionatefraction.
 4. The method of claim 3, wherein the second step is carriedout through fractional distillation.
 5. The method of claim 3, whereinthe second step is carried out utilizing an evaporator.
 6. The method ofclaim 1, wherein the first mixture is heated to a temperature of from50° C to 110° C.
 7. The method of claim 1, wherein the first mixture isheated to a temperature from about a reflux temperature of the firstmixture for a given reaction pressure to 20° C. below the refluxtemperature of the first mixture for the given reaction pressure duringstep (c).
 8. The method of claim 1, wherein the pressure in step (c)ranges from 0 PSIG to 125 PSIG.
 9. The method of claim 1, furthercomprising step (e) which occurs prior to step (d), and wherein step (e)includes a pH adjustment step.
 10. The method of claim 9, wherein the pHof the reaction mixture is adjusted to between 3 and
 6. 11. The methodof claim 1, wherein the hydroxyalkanoate containing compositioncomprises at least 3 percent by weight saccharide equivalents.
 12. Themethod of claim 1, wherein the hydroxyalkanoate containing compositioncomprises less than 10 percent by weight water.
 13. The method of claim1, wherein the catalyst is a solid acid catalyst, a Bronsted acidcatalyst, or a Lewis acid catalyst.
 14. The method of claim 1, wherein apressure below atmospheric pressure is utilized during step (d) torecover the alkyl hydroxypropionate fraction.
 15. The method of claim 1,wherein percent yield of alkyl hydroxypropionate from hydroxyalkanoateequivalents is greater than 50%.
 16. The method of claim 1, whereinpercent yield of alkyl hydroxypropionate from hydroxyalkanoateequivalents is greater than 90%.
 17. The method of claim 1, whereinpercent recovery of alkyl hydroxypropionate from hydroxyalkanoateequivalents is greater than 50%.
 18. The method of claim 1, whereinpercent recovery of alkyl hydroxypropionate from hvdroxyalkanoateequivalents is greater than 80%.